Table 3.

Gene therapy for epilepsy

Protein encoded by transgene	Vector	Time of treatment	Effects	References
Fibroblast growth factor 2 and brain-derived neurotrophic factor	HSV-1	Latency (4 days after epileptogenic insult [pilocarpine])	Antiepileptogenic: reduced seizure frequency and severity Disease-modifying: attenuated epileptogenesis- associated pathology; reduced cell loss, neuroinfammation and mossy fibre sprouting; increased neurogenesis	Paradiso et al. (2009)97 Bovolenta et al. (2010)98 Paradiso et al. (2011)99
γ-aminobutyric acid receptor A subunit α1	AAV2	Before epileptogenic insult (pilocarpine)	Antiseizure: decreased percentage of animals with spontaneous seizures	Raol et al. (2006)101
N-methyl-D-aspartate subunit NR1*	AAV2	Before inferior collicus stimulation	Antiseizure or proseizure, depending on promoter used and transduced cell type	Haberman et al. (2002)100
Galanin	AAV2	Before epileptogenic insult (kainate) Epileptic animals (fully kindled)	Antiseizure: increased seizure threshold, reduced seizure frequency and severity, reduced number of animals experiencing seizures Disease-modifying: reduced cell loss	Haberman et al. (2003)103 Lin et al. (2003)104 McCown et al. (2006)106
NPY	Chimaeric AAV1/2	Before epileptogenic insult (kainate or kindling) In chronic period (with spontaneous seizures) after epileptogenic insult (self-sustained status epilepticus)	Antiseizure: increased latency to seizure, reduced seizure frequency and duration, and slowed kindling development Disease-modifying: arrested disease progression No adverse reactions: no alterations in learning and memory, anxiety or locomotor activity	Richichi et al. (2004)105 Foti et al. (2007)107 Noe et al. (2008)108 Sorensen et al. (2009)109 Noe et al. (2010)110
NPY and NPY2R	Chimaeric AAV1/2	Before epileptogenic insult (kindling)	Antiseizure effects more potent than with NPY alone	Woldbye et al. (2010)111
Glial cell line-derived neurotrophic factor	AAV2	Before epileptogenic insult (kindling, self-sustained status epilepticus)	Antiseizure: increased seizure threshold, prevented seizure generalization, reduced seizure severity and mortality	Kanter-Schlifke et al (2007)152
Adenosine kinase*	AAV8	Epileptic animals (spontaneously seizing adenosine kinase transgenic mice)	Antiseizure: reduced frequency of spontaneous seizures	Theofilas et al. (2011)153
ICP10PK (antiapoptotic protein)	HSV-2	Before epileptogenic insult (kainate)	Antiseizure:prevented seizures Disease-modifying: prevented neuronal loss and inflammation	Laing et al. (2006)154
Voltage-gated potassium channel subunit Kv1.1	Lentivirus	During or after epileptogenic insult (tetanus toxin in motor cortex)	Antiepileptogenic: prevented epileptiform events after administration during epileptogenic insult Disease-modifying: reduced frequency of epileptiform events following administration in established epilepsy	Wykes et al. (2012)102

^*Antisense DNA.

Abbreviations: AAV, adeno-associated virus; HSV, herpes simplex virus; NPY, neuropeptide Y; NPY2R, NPY2 receptor.